The present invention relates to novel substituted 2-aminothiazoles useful as pharmaceutical agents, to methods for their production, to pharmaceutical compositions which include these compounds, and a pharmaceutically acceptable carrier, and to pharmaceutical methods of treatment. More particularly, the novel compounds of the present invention are dopamine agonists having selectivity for the presynaptic dopamine receptor, i e., an autoreceptor. The advantage of an autoreceptor agonist is that it modulates the activity of dopaminergic systems selectively, without the postsynaptic stimulation which is inherent to nonselective dopamine agonists.
Compounds of formula A ##STR1## wherein X represents amino, acylamino, guanidino, and N,N-di-lower-aminomethyleneamino; n is an integer from 1 to 3; and Y represents ##STR2## wherein W is phenyl or substituted phenyl, ##STR3## wherein Z is carboxy lower alkyl are disclosed in U.S. Pat. No. 4,564,678 as having antigastric secretion activity.
Compounds of formula B ##STR4## wherein R is a group of formula: ##STR5## linked with the sulfur atom by its second carbon atom are disclosed in U.S. Pat. No. 4,018,786 as having hypocholesterolemic and antiinflammatory activity.
Compounds of formula C ##STR6## are described by Vitali, T., et al, Farmaco. Ed. Sci, vol. 41, pages 483-498 (1986) as gastric secretion stimulants.
Compounds of formula D ##STR7## wherein R.sub.1 is hydrogen, --SCH.sub.3 or --S--C.sub.2 H.sub.5 ; and R.sub.2 is ##STR8## where R.sub.3 is methyl, phenyl, substituted phenyl, 2-pyridyl, or --CO.sub.2 C.sub.2 H.sub.5, ##STR9## are described by Bogdal, M., et al, Acta Polon. Pharm. XL, 1983(2), pages 159-170.
A series of 1-(thiazolyl-5-alkyl)-4-(pyridyl-2)piperazines which exhibit blood pressure lowering and CNS activity is disclosed in British Patent No. 1,149,110.
A series of substituted piperidine derivatives which exhibit tranquilizing activity is disclosed in U.S. Pat. No. 3,821,234.
However, none of the thiazoles disclosed in the aforementioned references suggest the combination of structural variations of the compounds of the present invention described hereinafter. Furthermore, the aforementioned thiazole derivatives are not disclosed as dopamione agonists having selectivity for the presynaptic dopamine receptor.